A Single-arm, Open-label, Multicenter Phase II Study of Cadonilimab Combined With Nab -Paclitaxel in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer Previously Treated With Immune Checkpoint Inhibitors
Overview
- Phase
- Phase 2
- Intervention
- Cadonilimab
- Conditions
- Uterine Cervical Neoplasms
- Sponsor
- Women's Hospital School Of Medicine Zhejiang University
- Enrollment
- 58
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase II trial of combination therapy of cadonilimab(Bispecific Anti-PD-1/CTLA-4 Antibody) plus nab-Paclitaxel in patients with recurrent or metastatic cervical cancer that had failed PD-1/PD-L1 blockade therapy. As a bispecific antibody against PD-1 and CTLA-4, cardonirimab can not only induce the production of a large number of T cells in the early stage of immune response by antagonizing CTLA-4, but also block PD-1 and PD-L1/L2 combination. Thereby restoring the killing function of T cells to tumor cells and reducing the exhaustion of T cells.The hypothesis is the combination of cadonilimab and nab-Paclitaxel will overcome PD-1/PD-L1 blockade-resistance to enhance the response of patients with persistant, recurrent or metastatic cervical cancer.
Detailed Description
Primary objective: Objective response rate for cadonilimab in combination with nab-paclitaxel in the treatment of persistent, recurrent, or metastatic cervical cancer previously treated with immune checkpoint inhibitors. Secondary objective: To evaluate duration of response (DoR) and disease control rate (DCR) of cardinirimab combined with nab-paclitaxel in the treatment of persistent, recurrent or metastatic cervical cancer who have previously received immune checkpoint inhibitor therapy based on RECIST v1.1 and time to response (TTR). To evaluate the progression-free survival (PFS) and overall survival (OS) of patients with persistent, recurrent or metastatic cervical cancer who had previously received immune checkpoint inhibitor therapy with cardonilimab combined with nab-paclitaxel. To evaluate the safety and tolerability of this combination therapy. Exploratory objective: To search for potential indicators in tumor tissue or peripheral blood of subjects that can predict the efficacy of cardonirimab combined with nab-paclitaxel.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects are autonomous and fully autonomous, understand and voluntarily sign a written informed consent within 30 days before enrollment.
- •Age ≥ 18 and ≤ 75 years old on the date of signing the informed consent form, female.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Expected survival period ≥ 3 months.
- •Persistent, recurrent or metastatic cervical cancer confirmed by histology or cytology.
- •Subjects who have previously failed treatment with PD-1, PD-L1 or CTLA4 inhibitors.
- •There is at least one measurable tumor lesion according to the RECIST v1.1 standard; tumor lesions in the previous radiotherapy area or other locoregional treatment sites are generally not regarded as measurable lesions, unless the lesion has definite progression and persists after 3 months of radiotherapy, Or the tumor nature of the lesion is confirmed by biopsy.
- •All subjects need to provide informed consent to provide freshly obtained tumor tissue samples or tumor tissue samples archived within 5 years (formalin-fixed paraffin-embedded \[FFPE\] tissue wax blocks or at least 5 unstained tumor tissue Biopsy samples, preferably freshly obtained tumor tissue samples). If the subject cannot provide the tumor tissue sample archived within 5 years before randomization or the tumor tissue sample is not suitable for use, a biopsy must be performed to collect fresh tumor tissue; if the investigator judges that there is a safety risk in the subject's tumor tissue biopsy, the Discuss with medical monitor.
- •The subject agrees to collect tumor tissue and peripheral blood samples required during the screening period and the research process and apply them to relevant research.
- •The results of laboratory tests after the screening period suggest that the subject has good organ function:
Exclusion Criteria
- •Suffering from other active malignant tumors within 3 years before randomization, except locally curable tumor types and those who have been cured, such as Squamous cell carcinoma of the skin, basal cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the breast.
- •Severe immunotherapy-related toxicity occurred during the previous anti-PD-1/PD-L1 monoclonal antibody treatment, including but not limited to: grade 3/4 pneumonia, proteinuria, uveitis or episcleritis, myasthenia gravis, Pancreatitis, hepatitis, bullous skin disease (including SJS, TEN); grade 2-4 encephalitis, myocarditis; any grade of Guillain-Barré syndrome, transverse myelitis; severe inflammation that significantly affects the quality of life of the patient sex joints.
- •Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, or other unmarketed clinical research drugs and other anti-tumor treatments within 4 weeks before the first use of the study drug.
- •Received nab-paclitaxel drug therapy within 6 months before the first use of the study drug. Known contraindications to nab-paclitaxel or hypersensitivity to any of its components.
- •Received drugs with immunomodulatory effects (such as thymosin, interferon, interleukin-2) within 2 weeks before randomization; received Chinese patent medicines with anti-tumor indications (such as Aidi injection, etc.) within 2 weeks before randomization.
- •Received major organ surgery (not including needle biopsy, etc.) or experienced significant trauma within 4 weeks before the first use of the study drug, or required elective surgery during the trial
- •There is central nervous system metastasis or cancerous meningitis.
- •Pleural effusion, pericardial effusion, or peritoneal effusion with uncontrollable need for repeated drainage (more than once a month) of subjects.
- •Suffering from active or recurrent autoimmune diseases; except the following: vitiligo, alopecia, psoriasis, or eczema that do not require systemic treatment; hypothyroidism caused by autoimmune thyroiditis that only requires stable doses of Hormone replacement therapy; type 1 diabetes requiring only a steady dose of insulin replacement therapy.
- •Subjects who need to use \> 10 mg/day prednisone or equivalent dose of glucocorticoid or other immunosuppressive drugs for systemic treatment within 14 days before randomization; except the following
Arms & Interventions
Cadonilimab plus nab-paclitaxel
Drug: Cadonilimab 10mg/kg,every 3 weeks,IV infusion Drug: Nab paclitaxel ≤260mg/m2,every 3 weeks,IV infusion
Intervention: Cadonilimab
Cadonilimab plus nab-paclitaxel
Drug: Cadonilimab 10mg/kg,every 3 weeks,IV infusion Drug: Nab paclitaxel ≤260mg/m2,every 3 weeks,IV infusion
Intervention: Nab paclitaxel
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: up to 2 years
To evaluate the clinical activity (as assessed by objective response rate \[ORR\]) of specific Cadonilimab and Nab-Paclitaxel combination.
Secondary Outcomes
- Incidence of adverse events(Day 1 of each cycle (each cycle is 21 days), up to 2 years)
- Duration of response(up to 2 years)
- Progression Free survival(up to 2 years)
- Disease control rate (DCR)(up to 2 years)
- Time to response (TTR)(up to 2 years)
- Overall survival(Cycle 1 Day 1, Day 1 of each cycle (each cycle is 21 days), every 12 weeks after end of treatment)
- Health-Related Quality of Life (HRQoL) Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQC30) Score(At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length of 21 days), and at the post-treatment visit (up to 2 years))